Efficacy and predictive factors of transarterial chemoembolization combined with lenvatinib plus programmed cell death protein-1 inhibition for unresectable hepatocellular carcinoma

BACKGROUND The efficacy and safety of transarterial chemoembolization(TACE)combined with lenvatinib plus programmed cell death protein-1(PD-1)for unresectable hepato-cellular carcinoma(HCC)have rarely been evaluated and it is unknown which factors are related to efficacy.AIM To evaluate the efficacy and independent predictive factors of TACE combined with lenvatinib plus PD-1 inhibitors for unresectable HCC.METHODS This study retrospectively enrolled patients with unresectable HCC who received TACE/lenvatinib/PD-1 treatment between March 2019 and April 2022.Overall survival(OS)and progression-free survival(PFS)were determined.The objective response rate(ORR)and disease control rate(DCR)were evaluated in accordance with the modified Response Evaluation Criteria in Solid Tumors.Additionally,the prognostic factors affecting the clinical outcome were assessed.RESULTS One hundred and two patients were enrolled with a median follow-up duration of 12.63 months.The median OS was 26.43 months(95%CI:17.00-35.87),and the median PFS was 10.07 months(95%CI:8.50-11.65).The ORR and DCR were 61.76%and 81.37%,respectively.The patients with Barcelona Clinic Liver Cancer Classification(BCLC)B stage,early neutrophil-to-lymphocyte ratio(NLR)response(decrease),or early alpha-fetoprotein(AFP)response(decrease>20%)had superior OS and PFS than their counterparts.CONCLUSION This study showed that TACE/lenvatinib/PD-1 treatment was well tolerated with encouraging efficacy in patients with unresectable HCC.The patients with BCLC B-stage disease with early NLR response(decrease)and early AFP response(decrease>20%)may achieve better clinical outcomes with this triple therapy.

Computed tomography radiomic features and clinical factors predicting the response to first transarterial chemoembolization in intermediate-stage hepatocellular carcinoma

Background:According to clinical practice guidelines,transarterial chemoembolization(TACE)is the standard treatment modality for patients with intermediate-stage hepatocellular carcinoma(HCC).Early prediction of treatment response can help patients choose a reasonable treatment plan.This study aimed to investigate the value of the radiomic-clinical model in predicting the efficacy of the first TACE treatment for HCC to prolong patient survival.Methods:A total of 164 patients with HCC who underwent the first TACE from January 2017 to September 2021 were analyzed.The tumor response was assessed by modified response evaluation criteria in solid tumors(mRECIST),and the response of the first TACE to each session and its correlation with overall survival were evaluated.The radiomic signatures associated with the treatment response were identified by the least absolute shrinkage and selection operator(LASSO),and four machine learning models were built with different types of regions of interest(ROIs)(tumor and corresponding tissues)and the model with the best performance was selected.The predictive performance was assessed with receiver operating characteristic(ROC)curves and calibration curves.Results:Of all the models,the random forest(RF)model with peritumor(+10 mm)radiomic signatures had the best performance[area under ROC curve(AUC)=0.964 in the training cohort,AUC=0.949 in the validation cohort].The RF model was used to calculate the radiomic score(Rad-score),and the optimal cutoff value(0.34)was calculated according to the Youden’s index.Patients were then divided into a high-risk group(Rad-score>0.34)and a low-risk group(Rad-score≤0.34),and a nomogram model was successfully established to predict treatment response.The predicted treatment response also allowed for significant discrimination of Kaplan-Meier curves.Multivariate Cox regression identified six independent prognostic factors for overall survival,including male[hazard ratio(HR)=0.500,95%confidence interval(CI):0.260–0.962,P=0.038],alpha-fetoprotein(HR=1.003,95%CI:1.002–1.004,P<0.001),alanine aminotransferase(HR=1.003,95%CI:1.001–1.005,P=0.025),performance status(HR=2.400,95%CI:1.200–4.800,P=0.013),the number of TACE sessions(HR=0.870,95%CI:0.780–0.970,P=0.012)and Rad-score(HR=3.480,95%CI:1.416–8.552,P=0.007).Conclusions:The radiomic signatures and clinical factors can be well-used to predict the response of HCC patients to the first TACE and may help identify the patients most likely to benefit from TACE.

Meta-analysis of transarterial chemoembolization combined with cryoablation vs transarterial chemoembolization alone for≥5 cm hepatocellular carcinoma

BACKGROUND Hepatocellular carcinoma(HCC)ranks sixth globally in cancer incidence and third in mortality rates.Unfortunately,over 70% of HCC patients forego the opportunity for curative surgery or liver transplantation due to inadequate physical examinations,poor physical condition,and limited organ availability upon diagnosis.Clinical guidelines endorse transarterial chemoembolization(TACE)as the frontline treatment for intermediate to advanced-stage HCC.Cryoablation(CRA)is an emerging local ablative therapy increasingly used in HCC management.Recent studies suggest that combining CRA with TACE offers complementary and synergistic effects,potentially improving long-term survival rates.However,the superiority of combined TACE+CRA therapy over TACE alone for HCC lesions equal to or exceeding 5 cm requires further investigation.AIM To compare the efficacy and safety of TACE combined with CRA vs TACE alone in the treatment of HCC with a diameter of≥5 cm.METHODS PubMed,EMBASE,Cochrane Library,CNKI,Wanfang,and VIP databases were searched to retrieve all relevant studies on TACE and CRA up to July 2022.Meta-analysis was performed using RevMan 5.3 software.RESULTS After screening according to the inclusion and exclusion criteria,6 articles were included,including 2 randomized controlled trials and 4 nonrandomized controlled trials,with a total of 575 patients included in the meta-analysis.The results showed that the objective response rate[odds ratio(OR)=2.56,95%confidence interval(CI):1.66-3.96,P<0.0001],disease control rate(OR=3.03,95%CI:1.88-4.89,P<0.00001),1-year survival rate(OR=3.79,95%CI:2.50-5.76,P<0.00001),2-year survival rate(OR=2.34,95%CI:1.43-3.85,P=0.0008),and 3-year survival rate(OR=3.34,95%CI:1.61-6.94,P=0.001)were all superior to those of the control group;the postoperative decrease in alpha-fetoprotein value(OR=295.53,95%CI:250.22-340.85,P<0.0001),the postoperative increase in CD4 value(OR=10.59,95%CI:8.78-12.40,P<0.00001),and the postoperative decrease in CD8 value(OR=6.47,95%CI:4.44-8.50,P<0.00001)were also significantly higher than those in the TACE-alone treatment group.CONCLUSION Compared with TACE-alone treatment,TACE+CRA combined treatment not only improves the immune function of HCC patients with a diameter of≥5 cm,but also enhances the therapeutic efficacy and long-term survival rate,without increasing the risk of complications.Therefore,TACE+CRA combined treatment may be a more recommended treatment for patients with HCC with a diameter of≥5 cm.

Nomogram model based onγ-glutamyl transferase to albumin ratio predicts survival in hepatocellular carcinoma patients with transarterial chemoembolization treatment

BACKGROUND The development of tumor is closely linked to inflammation.Therefore,targeting molecules involved in inflammation may be effective in predicting cancer prognosis.Transarterial chemoembolization(TACE)holds significant therapeutic significance in addressing hepatocellular carcinoma(HCC).At present,no studies have evaluated the predictive value ofγ-glutamyl transferase to albumin ratio(GAR)on the prognosis of HCC undergoing TACE.AIM To explore the potential prognostic significance of the GAR in individuals undergoing TACE for HCC.METHODS A total of 1231 patients from seven hospitals in China were randomized into a training cohort(n=862)and a validation cohort(n=369).To establish inde pendent prognostic factors for overall survival(OS),we utilized multivariate and univariate Cox regression models.The best cut-off value of the GAR was determined with the X-tile software,with OS as the basis.Validations were performed using dual therapy cohort and triple therapy cohort.RESULTS X-tile software revealed a GAR threshold of 4.75 as optimal.Both pre-and post-propensity score matching analyses demonstrated that the median OS in the low-GAR group(<4.75)was notably longer compared to the high-GAR group(≥4.75),showing results of 26.9 vs 9.8 months(P<0.001)initially,and 18.1 vs 11.3 months(P<0.001)after match.Furthermore,multivariate analysis identified GAR≥4.75 as an independent prognostic factor(P<0.001).The receiver operating characteristic curves for the nomogram showed area under receiver operating characteristic curves of 0.741,0.747,and 0.708 for predicting 1-,2-,and 3-year survival,respectively.Consistent findings were reiterated in the two cohorts involving TACE in combination with targeted therapy and TACE in combination with targeted therapy and immunotherapy.Calibration curve and decision curve analyses substantiated the model’s relatively robust predictive capabilities.CONCLUSION Our study validates the effective prognostic capacity of the GAR-based nomogram for HCC patients undergoing TACE or TACE in combination with systemic therapy.

Drug-eluting bead transarterial chemoembolization as neoadjuvant therapy pre-liver transplantation for advanced-stage hepatocellular carcinoma

BACKGROUND The objectives of this study were to assess the safety and efficacy of drug-eluting bead transarterial chemoembolization(DEB-TACE)as neoadjuvant therapy before liver transplantation(LT)for advanced-stage hepatocellular carcinoma(HCC)and to analyze the prognostic factors.AIM To determine whether DEB-TACE before LT is superior to LT for advanced-stage HCC.METHODS A total of 99 individuals diagnosed with advanced HCC were studied retrospectively.The participants were categorized into the following two groups based on whether they had received DEB-TACE before LT:DEB-TACE group(n=45)and control group(n=54).The participants were further divided into two subgroups based on the presence or absence of segmental portal vein tumor thrombus(PVTT).The DEB-TACE group consisted of two subgroups:Group A(n=31)without PVTT and group B(n=14)with PVTT.The control group also had two subgroups:Group C(n=37)without PVTT and group D(n=17)with PVTT.Data on patient demographics,disease characteristics,therapy response,and adverse events(AEs)were collected.The overall survival(OS)and recurrence-free survival(RFS)rates were assessed using Kaplan-Meier curves.Univariate and multivariate Cox regression analyses were conducted to determine the parameters that were independently related to OS and RFS.RESULTS The DEB-TACE group exhibited an overall response rate of 86.6%.Following therapy,there was a significant decrease in the median alpha-fetoprotein(AFP)level(275.1 ng/mL vs 41.7 ng/mL,P<0.001).The main AE was post-embolization syndrome.The 2-year rates of RFS and OS were significantly higher in the DEB-TACE group than in the control group(68.9%vs 38.9%,P=0.003;86.7%vs 63.0%,P=0.008).Within the subgroups,group A had higher 2-year rates of RFS and OS compared to group C(71.0%vs 45.9%,P=0.038;83.8%vs 62.2%,P=0.047).The 2-year RFS rate of group B was markedly superior to that of group D(64.3%vs 23.5%,P=0.002).Results from multivariate analyses showed that pre-LT DEB-TACE[hazard ratio(HR)=2.73,95%confidence interval(CI):1.44-5.14,P=0.04],overall target tumor diameter≤7 cm(HR=1.98,95%CI:1.05-3.75,P=0.035),and AFP level≤400 ng/mL(HR=2.34;95%CI:1.30-4.19,P=0.009)were significant risk factors for RFS.Additionally,pre-LT DEBTACE(HR=3.15,95%CI:1.43-6.96,P=0.004)was identified as a significant risk factor for OS.CONCLUSION DEB-TACE is a safe and efficient therapy for advanced-stage HCC and also enhances patient survival after LT.

Present and prospect of transarterial chemoembolization combined with tyrosine kinase inhibitor and PD-1 inhibitor for unresectable hepatocellular carcinoma

In this editorial,we comment on the article(World J Gastrointest Oncol 2024;16:1236-1247),which is a retrospective study of transarterial chemoembolization(TACE)combined with multi-targeted tyrosine kinase inhibitor(TKI)and programmed cell death protein-1(PD-1)inhibitor for the treatment of unresectable hepatocellular carcinoma(HCC).Herein,we focus specifically on the mechanisms of this triple therapy,administration sequence and selection of each medication,and implications for future clinical trials.Based on the interaction mechanisms between medications,the triple therapy of TACE+TKI+PD-1 is proposed to complement the deficiency of each monotherapy,and achieve synergistic antitumor effects.Although this triple therapy has been evaluated by several retrospective trials,it is still controversial whether the triple therapy achieves better clinical benefits,due to the flawed study design and heterogeneity in medications.In addition,the administration sequence,which may greatly affect the clinical benefit,needs to be fully considered at clinical decision-making for obtaining better prognosis.We hope that this editorial could contribute to the design and optimization of future trials.

Unresectable hepatocellular carcinoma:Transarterial chemoembolization combined with lenvatinib in combination with programmed death-1 inhibition is a possible approach

In this editorial,we review the article“Efficacy and predictive factors of transarterial chemoembolization combined with lenvatinib plus programmed cell death protein-1 inhibition for unresectable hepatocellular carcinoma”.We specifically focused on whether transarterial chemoembolization combined with lenvatinib in combination with a programmed death 1 inhibitor could be used in patients with unresectable hepatocellular carcinoma.Since both transarterial chemoembolization as well as lenvatinib in combination with programmed death 1 inhibitors play an important role in the treatment of advanced liver cancer,but the combination of all three therapeutic approaches needs more research.

Paravertebral block's effect on analgesia and inflammation in advanced gastric cancer patients undergoing transarterial chemoembolization and microwave ablation

BACKGROUND Transarterial chemoembolization(TACE)combined with microwave ablation(MWA)is an effective treatment strategy for patients with advanced gastric cancer and liver metastasis.However,it may cause severe postoperative pain and inflammatory responses.The paravertebral block(PVB)is a regional anesthetic technique that provides analgesia to the thoracic and abdominal regions.AIM To evaluate the effect of PVB on postoperative analgesia and inflammatory response in patients undergoing TACE combined with MWA for advanced gastric cancer and liver metastasis.METHODS Sixty patients were randomly divided into PVB and control groups.The PVB group received ultrasound-guided PVB with 0.375%ropivacaine preoperatively,whereas the control group received intravenous analgesia with sufentanil.The primary outcome was the visual analog scale(VAS)score for pain at 6 h,12 h,24 h,and 48 h after the procedure.Secondary outcomes were the dose of sufentanil used,incidence of adverse events,and levels of inflammatory markers(white blood cell count,neutrophil percentage,C-reactive protein,and procalcitonin)before and after the procedure.RESULTS The PVB group had significantly lower VAS scores at 6 h,12 h,24 h,and 48 h after the procedure compared with the control group(P<0.05).The PVB group also had a significantly lower consumption of sufentanil and a lower incidence of nausea,vomiting,and respiratory depression than did the control group(P<0.05).Compared with the control group,the PVB group had significantly lower levels of inflammatory markers 24 h and 48 h after the procedure(P<0.05).CONCLUSION PVB can effectively reduce postoperative pain and inflammatory responses and improve postoperative comfort and recovery in patients with advanced gastric cancer and liver metastasis treated with TACE combined with MWA.

Sorafenib plus transarterial chemoembolization vs sorafenib alone for patients with advanced hepatocellular carcinoma: A systematic review and meta-analysis

BACKGROUND Although the past decade has seen remarkable advances in treatment options for hepatocellular carcinoma(HCC),the dismal overall prognosis still envelops HCC patients.Several comparative trials have been conducted to study whether transarterial chemoembolization(TACE)could improve clinical outcomes in patients receiving sorafenib for advanced HCC;however,the findings have been inconsistent.AIM To study the potential synergies and safety of sorafenib plus TACE vs sorafenib alone for treating advanced HCC,by performing a systematic review and metaanalysis.METHODS This study was conducted following the PRISMA statement.A systematic literature search was conducted using the Cochrane Library,Embase,PubMed,and Web of Science databases.Data included in the present work were collected from patients diagnosed with advanced HCC receiving sorafenib plus TACE or sorafenib alone.Data synthesis and meta-analysis were conducted using Review Manager software.RESULTS The present study included 2780 patients from five comparative clinical trials(1 was randomized control trial and 4 were retrospective studies).It was found that patients receiving sorafenib plus TACE had better prognoses in terms of overall survival(OS),with a combined hazard ratio(HR)of 0.65[95%confidence interval(95%CI):0.46–0.93,P=0.02,n=2780].Consistently,progression free survival(PFS)and time to progression(TTP)differed significantly between the sorafenib plus TACE arm and sorafenib arm(PFS:HR=0.62,95%CI:0.40–0.96,P=0.03,n=443;TTP:HR=0.73,95%CI:0.64-0.83,P<0.00001,n=2451).Disease control rate(DCR)was also significantly increased by combination therapy(risk ratio=1.36,95%CI:1.02-1.81,P=0.04,n=641).Regarding safety,the incidence of any adverse event(AE)was increased due to the addition of TACE;however,no significant difference was found in grade≥3 AEs.CONCLUSION The combination of sorafenib with TACE has superior efficacy to sorafenib monotherapy,as evidenced by prolonged OS,PFS,and TTP,as well as increased DCR.Additional high-quality trials are essential to further validate the clinical benefit of this combination in the treatment of advanced HCC.

Clinical efficacy of Gamma Knife® combined with transarterial chemoembolization and immunotherapy in the treatment of primary liver cancer

BACKGROUND This study was designed to investigate the clinical efficacy and safety of Gamma Knife®combined with transarterial chemoembolization(TACE)and immunotherapy in the treatment of primary liver cancer.AIM To investigate the clinical efficacy and safety of Gamma Knife®combined with TACE and immune-targeted therapy in the treatment of primary liver cancer.METHODS Clinical data from 51 patients with primary liver cancer admitted to our hospital between May 2018 and October 2022 were retrospectively collected.All patients underwent Gamma Knife®treatment combined with TACE and immunotherapy.The clinical efficacy,changes in liver function,overall survival(OS),and progression-free survival(PFS)of patients with different treatment responses were evaluated,and adverse reactions were recorded.RESULTS The last follow-up for this study was conducted on October 31,2023.Clinical evaluation of the 51 patients with primary liver cancer revealed a partial response(PR)in 27 patients,accounting for 52.94%(27/51);stable disease(SD)in 16 patients,accounting for 31.37%(16/51);and progressive disease(PD)in 8 patients,accounting for 15.69%(8/51).The objective response rate was 52.94%,and the disease control rate was 84.31%.Alanine aminotransferase,aspartate aminotransferase,lactate dehydrogenase,and alpha-fetoprotein isoform levels decreased after treatment compared with pretreatment(all P=0.000).The median OS was 26 months[95%confidence interval(95%CI):19.946-32.054]in the PR group and 19 months(95%CI:14.156-23.125)in the SD+PD group,with a statistically significant difference(P=0.015).The median PFS was 20 months(95%CI:18.441-34.559)in the PR group and 12 months(95%CI:8.745-13.425)in the SD+PD group,with a statistically significant difference(P=0.002).Common adverse reactions during treatment included nausea and vomiting(39.22%),thrombocytopenia(27.45%),and leukopenia(25.49%),with no treatment-related deaths reported.CONCLUSION Gamma Knife®combined with TACE and immune-targeted therapy is safe and effective in the treatment of primary liver cancer and has a good effect on improving the clinical benefit rate and liver function of patients.

Combined transarterial chemoembolization and tislelizumab for patients with unresectable hepatocellular carcinoma

BACKGROUND Hepatocellular carcinoma(HCC)often presents as unresectable,necessitating effective treatment modalities.Combining transarterial chemoembolization(TACE)with immunotherapy and targeted therapy has shown promise,yet real-world evidence is needed.AIM To investigate effectiveness and safety of TACE with tislelizumab±targeted therapy for unresectable HCC in real-world setting.METHODS This retrospective study included patients with unresectable HCC receiving combined treatment of TACE and tislelizumab.The clinical outcomes included progression-free survival(PFS),overall survival(OS),objective response rate(ORR),and disease control rate(DCR).All patients were evaluated according to the mRECIST criteria.The adverse event(AE)was also assessed.RESULTS In this study of 56 patients with median follow-up of 10.9 months,7 had previous immunotherapy.Tislelizumab was administered before TACE in 21(37.50%)and after in 35(62.50%)patients,with 91.07%receiving concurrent targeted therapy.Median PFS was 14.0(95%CI:7.0-18.00)months,and OS was 28(95%CI:2.94-53.05)months.Patients with prior immunotherapy had shorter PFS(6 vs.18 months,P=0.006).Overall ORR and DCR were 82.14%and 87.50%.Grade≥3 treatment-related AEs included increased alanine aminotransferase(8.93%),aspartate aminotransferase(10.71%),and total bilirubin(3.57%).CONCLUSION The combination of TACE and tislelizumab,with or without targeted therapy,demonstrated promising efficacy and safety in unresectable HCC,especially in immunotherapy-naive patients,warranting further prospective validation studies.

Transarterial chemoembolization plus stent placement for hepatocellular carcinoma with main portal vein tumor thrombosis:A meta-analysis

BACKGROUND Portal vein tumor thrombus is an important indicator of poor prognosis in patients with hepatocellular carcinoma.Transarterial chemoembolization is recommended as the standard first-line therapy for unresectable hepatocellular carcinoma.Portal vein stent placement is a safe and effective therapy for promptly restoring flow and relieving portal hypertension caused by tumor thrombus.AIM To assess the clinical significance of transarterial chemoembolization plus stent placement for the treatment of hepatocellular carcinoma with main portal vein tumor thrombosis.METHODS We searched English and Chinese databases,assessed the quality of the included studies,analyzed the characteristic data,tested heterogeneity,explored heterogeneity,and tested publication bias.RESULTS In total,eight clinical controlled trials were included.The results showed that the pressure in the main portal vein after stent placement was significantly lower than that with no stent placement.The cumulative stent patency and survival rates at 6 and 12 months were lower in the transarterial chemoembolization+stent placement group than in the transarterial chemoembolization+stent placement+brachytherapy/radiotherapy group.The survival rates of patients treated with transarterial chemoembolization+stent placement for 6 and 12 months were higher than those of patients treated with transarterial chemoembolization alone.CONCLUSION For Chinese patients with hepatocellular carcinoma with main portal vein tumor thrombosis,transarterial chemoembolization plus stenting is effective.Transarterial chemoembolization+stent placement is more effective than transarterial chemoembolization alone.Transarterial chemoembolization+stent placement+brachytherapy/radiotherapy is more effective than transarterial chemoembolization+stenting.

Advances in Research of Post Embolism Syndrome after Transarterial Chemoembolization(TACE)for Hepatocellular Carcinoma

This article reviews the concept and clinical manifestations of post embolism syndrome after transarterial chemoembolization(TACE),and the prevention or timely intervention of post embolism syndrome in advance is expected to reduce its incidence and degree in clinical treatment,and to improve the quality of treatment of Hepatocellular Carcinoma Carcinoma(HCC).

Efficacy of dexamethasone and N-acetylcysteine combination in preventing post-embolization syndrome after transarterial chemoembolization in hepatocellular carcinoma

BACKGROUND Conventional transarterial chemoembolization(cTACE)is the current standard treatment for intermediate-stage hepatocellular carcinoma(HCC).Postembolization syndrome(PES)is complex clinical syndrome that presents as fever,abdominal pain,nausea,and vomiting.Either dexamethasone(DEXA)or Nacetylcysteine(NAC)is used to prevent PES;however,the synergistic effect of their combined therapy for preventing PES and liver decompensation has not been determined.AIM To evaluate the efficacy of DEXA and NAC combination in preventing PES and liver decompensation after cTACE.METHODS Patients with Barcelona Clinic Liver Cancer stage A or B HCC who were scheduled for TACE were prospectively enrolled.All patients were randomly stratified to receive NAC and DEXA or placebo.The dual therapy(NAC+DEXA)group received intravenous administration of 10 mg DEXA every 12 h,NAC 24 h prior to cTACE(150 mg/kg/h for 1 h followed by 12.5 mg/kg/h for 4 h),and a continuous infusion of 6.25 mg/h NAC plus 4 mg DEXA every 12 h for 48 h after cTACE.The placebo group received an infusion of 5%glucose solution until 48 h after procedure.PES was defined by South West Oncology Group toxicity code grading of more than 2 that was calculated using incidence of fever,nausea,vomiting,and pain.RESULTS One-hundred patients were enrolled with 50 patients in each group.Incidence of PES was significantly lower in the NAC+DEXA group compared with in the placebo group(6%vs 80%;P<0.001).Multivariate analysis showed that the dual treatment is a protective strategic therapy against PES development[odds ratio(OR)=0.04;95%confidence interval(CI):0.01-0.20;P<0.001).Seven(14%)patients in the placebo group,but none in the NAC+DEXA group,developed post-TACE liver decompensation.A dynamic change in Albumin-Bilirubin score of more than 0.5 point was found to be a risk factor for post-TACE liver decompensation(OR=42.77;95%CI:1.01-1810;P=0.049).CONCLUSION Intravenous NAC+DEXA administration ameliorated the occurrence of PES event after cTACE in patients with intermediate-stage HCC.

Clinical-radiomics predictors to identify the suitability of transarterial chemoembolization treatment in intermediate-stage hepatocellular carcinoma:A multicenter study

Background: Although transarterial chemoembolization(TACE) is the first-line therapy for intermediatestage hepatocellular carcinoma(HCC), it is not suitable for all patients. This study aimed to determine how to select patients who are not suitable for TACE as the first treatment choice. Methods: A total of 243 intermediate-stage HCC patients treated with TACE at three centers were retrospectively enrolled, of which 171 were used for model training and 72 for testing. Radiomics features were screened using the Spearman correlation analysis and the least absolute shrinkage and selection operator(LASSO) algorithm. Subsequently, a radiomics model was established using extreme gradient boosting(XGBoost) with 5-fold cross-validation. The Shapley additive explanations(SHAP) method was used to visualize the radiomics model. A clinical model was constructed using univariate and multivariate logistic regression. The combined model comprising the radiomics signature and clinical factors was then established. This model’s performance was evaluated by discrimination, calibration, and clinical application. Generalization ability was evaluated by the testing cohort. Finally, the model was used to analyze overall and progression-free survival of different groups. Results: A third of the patients(81/243) were unsuitable for TACE treatment. The combined model had a high degree of accuracy as it identified TACE-unsuitable cases, at a sensitivity, specificity, and area under the receiver operating characteristic curve(AUC) of 0.759, 0.885, 0.906 [95% confidence interval(CI): 0.859-0.953] in the training cohort and 0.826, 0.776, and 0.894(95% CI: 0.815-0.972) in the testing cohort, respectively. Conclusions: The high degree of accuracy of our clinical-radiomics model makes it clinically useful in identifying intermediate-stage HCC patients who are unsuitable for TACE treatment.

Clinical outcomes of lenvatinib plus transarterial chemoembolization with or without programmed death receptor-1 inhibitors in unresectable hepatocellular carcinoma

BACKGROUND Programmed death receptor-1(PD-1)inhibitors have been approved as secondline treatment regimen in hepatocellular carcinoma(HCC),but it is still worth studying whether patients can benefit from PD-1 inhibitors as first-line drugs combined with targeted drugs and locoregional therapy.AIM To estimate the clinical outcome of transarterial chemoembolization(TACE)and lenvatinib plus PD-1 inhibitors for patients with unresectable HCC(uHCC).METHODS We carried out retrospective research of 65 patients with uHCC who were treated at Peking Union Medical College Hospital from September 2017 to February 2022.45 patients received the PD-1 inhibitors,lenvatinib,TACE(PD-1-Lenv-T)therapy,and 20 received the lenvatinib,TACE(Lenv-T)therapy.In terms of the dose of lenvatinib,8 mg was given orally for patients weighing less than 60 kg and 12 mg for those weighing more than 60 kg.Of the patients in the PD-1 inhibitor combination group,15 received Toripalimab,14 received Toripalimab,14 received Camrelizumab,4 received Pembrolizumab,9 received Sintilimab,and 2 received Nivolumab,1 with Tislelizumab.According to the investigators’assessment,TACE was performed every 4-6 wk when the patient had good hepatic function(Child-Pugh class A or B)until disease progression occurred.We evaluated the efficacy by the modified Response Evaluation Criteria in Solid Tumors(mRECIST criteria).We accessd the safety by the National Cancer Institute Common Terminology Criteria for Adverse Events,v 5.0.The key adverse events(AEs)after the initiation of combination therapy were observed.RESULTS Patients with uHCC who received PD-1-Lenv-T therapy(n=45)had a clearly longer overall survival than those who underwent Lenv-T therapy(n=20,26.8 vs 14.0 mo;P=0.027).The median progression-free survival time between the two treatment regimens was also measured{11.7 mo[95%confidence interval(CI):7.7-15.7]in the PD-1-Lenv-T group vs 8.5 mo(95%CI:3.0-13.9)in the Lenv-T group(P=0.028)}.The objective response rates of the PD-1-Lenv-T group and Lenv-T group were 44.4%and 20%(P=0.059)according to the mRECIST criteria,meanwhile the disease control rates were 93.3%and 64.0%(P=0.003),respectively.The type and frequency of AEs showed little distinction between patients received the two treatment regimens.CONCLUSION Our results suggest that the early combination of PD-1 inhibitors has manageable toxicity and hopeful efficacy in patients with uHCC.

The effect of adjuvant transarterial chemoembolization for hepatocellular carcinoma after liver resection based on risk stratification

Background:There is currently no standard adjuvant treatment proven to prevent hepatocellular carcinoma(HCC)recurrence.Recent studies suggest that postoperative adjuvant transarterial chemoembolization(PA-TACE)is beneficial for patients at high risk of tumor recurrence.However,it is difficult to select the patients.The present study aimed to develop an easy-to-use score to identify these patients.Methods:A total of 4530 patients undergoing liver resection were recruited.Independent risk factors were identified by Cox regression model in the training cohort and the Primary liver cancer big data transarterial chemoembolization(PDTE)scoring system was established.Results:The scoring system was composed of ten risk factors including alpha-fetoprotein(AFP),albuminbilirubin(ALBI)grade,operative bleeding loss,resection margin,tumor capsular,satellite nodules,tumor size and number,and microvascular and macrovascular invasion.Using 5 points as risk stratification,the patients with PA-TACE had higher recurrence-free survival(RFS)compared with non-TACE in>5 points group(P<0.001),whereas PA-TACE patients had lower RFS compared with non-TACE in≤5 points group(P=0.013).In the training and validation cohorts,the C-indexes of PDTE scoring system were 0.714[standard errors(SE)=0.010]and 0.716(SE=0.018),respectively.Conclusions:The model is a simple tool to identify PA-TACE for HCC patients after liver resection with a favorable performance.Patients with>5 points may benefit from PA-TACE.

ASARA,a prediction model based on Child-Pugh class in hepatocellular carcinoma patients undergoing transarterial chemoembolization

Background:Due to the high heterogeneity among hepatocellular carcinoma(HCC)patients receiving transarterial chemoembolization(TACE),the prognosis of patients varies significantly.The decisionmaking on the initiation and/or repetition of TACE under different liver functions is a matter of concern in clinical practice.Thus,we aimed to develop a prediction model for TACE candidates using risk stratification based on varied liver function.Methods:A total of 222 unresectable HCC patients who underwent TACE as their only treatment were included in this study.Cox proportional hazards regression was performed to select the independent risk factors and establish a predictive model for the overall survival(OS).The model was validated in patients with different Child-Pugh class and compared to previous TACE scoring systems.Results:The five independent risk factors,including alpha-fetoprotein(AFP)level,maximal tumor size,the increase of albumin-bilirubin(ALBI)grade score,tumor response,and the increase of aspartate aminotransferase(AST),were used to build a prognostic model(ASARA).In the training and validation cohorts,the OS of patients with ASARA score≤2 was significantly higher than that of patients with ASARA score>2(P<0.001,P=0.006,respectively).The ASARA model and its modified version“AS(ARA)”can effectively distinguish the OS(P<0.001,P=0.004)between patients with Child-Pugh class A and B,and the C-index was 0.687 and 0.706,respectively.For repeated TACE,the ASARA model was superior to Assessment for Retreatment with TACE(ART)and ALBI grade,maximal tumor size,AFP,and tumor response(ASAR)among Child-Pugh class A patients.For the first TACE,the performance of AS(ARA)was better than that of modified hepatoma arterial-embolization prognostic(mHAP),mHAP3,and ASA(R)models among Child-Pugh class B patients.Conclusions:The ASARA scoring system is valuable in the decision-making of TACE repetition for HCC patients,especially Child-Pugh class A patients.The modified AS(ARA)can be used to screen the ideal candidate for TACE initiation in Child-Pugh class B patients with poor liver function.

Short-term efficacy assessment of transarterial chemoembolization combined with radioactive iodine therapy in primary hepatocellular carcinoma

BACKGROUND Transarterial chemoembolization(TACE)is an effective treatment for primary hepatocellular carcinoma(PHC).Radioactive iodine therapy has been used in the treatment of advanced PHC,especially in patients with portal vein tumor thrombosis.However,data on the therapeutic effect of TACE combined with radioactive iodine therapy in PHC are scarce.AIM To investigate the clinical efficacy of TACE combined with radioactive iodine implantation therapy in advanced PHC via perfusion computed tomography(CT).METHODS For this study,98 advanced PHC patients were recruited and divided randomly into the study and control groups.Patients in the study group were treated with TACE combined radioactive iodine implantation therapy.Patients in the control group were treated with only TACE.The tumor lesion length,clinical effect,serum alpha-fetoprotein(AFP)and CT perfusion parameters were compared before and after therapy,and statistical analysis was performed.RESULTS There was no significant difference in tumor length and serum AFP between the study and control groups(P>0.05)before treatment.However,the tumor length and serum AFP in the study group were lower than those in the control group 1 mo and 3 mo after therapy.After 3 mo of treatment,the complete and partial remission rate of the study group was 93.88%,which was significantly higher than the control group(77.55%)(P<0.05).Before treatment,there were no significant differences between the two groups on the perfusion CT variables,including the lesion blood volume,permeability surface,blood flow,hepatic artery flow and mean transit time(P>0.05).After 3 mo of treatment,all perfusion CT variables were lower in the study group compared to the control group(P<0.05).The survival time of patients in the study group was 22 mo compared to 18 mo in the control group,which was significantly different[log rank(Mantel-Cox)=4.318,P=0.038].CONCLUSION TACE combined with radioactive iodine implantation in the treatment of advanced PHC can inhibit the formation of blood vessels in tumor tissue and reduce the perfusion level of tumor lesions,thereby improving the clinical efficacy and prolonging the survival time of patients.

Hypothetical hypoxia-driven rapid disease progression in hepatocellular carcinoma post transarterial chemoembolization:A case report

BACKGROUND Transarterial chemoembolization(TACE)is widely performed for intermediatestage or unresectable hepatocellular carcinoma(HCC),but approximately half of patients do not respond to TACE treatment.We describe a case of rapidly progressing of HCC after TACE and provide a possible hypothesis for this condition.The finding may contribute to identifying patients who obtain less benefit from TACE,thus avoiding the unnecessary waste of medical resources and treatment during the golden hour window.CASE SUMMARY A 61-year-old woman had been diagnosed with chronic hepatitis B infection and HCC at Barcelona Clinic Liver Cancer stage B,which had been treated by segmental hepatectomy 14 mo ago.The tumor recurred in the two months after surgery.She received an initial TACE and then underwent systemic therapy with lenvatinib 8 mg daily due to an increased level of alpha-fetoprotein(AFP)after the first TACE.However,the tumor continued to progress with an increased level of AFP,and she underwent a second TACE,after which the tumor volume did not obviously decrease on the contrast-enhanced computed tomography image.One month later,she had a third TACE to control the residual HCC tumors.Two weeks after that,the HCC had increased dramatically with tea-colored urine and yellowish skin turgor.Eventually,the patient refused further treatment and went into hospice care.CONCLUSION Intense hypoxia induced by TACE can trigger rapid disease progression in infiltrative HCC patients with a large tumor burden.